Posts Tagged brain

Imagine that the New Year has just begun. You’ve made a resolution to improve your physical fitness. In particular, you want to improve your muscle strength. You’ve heard that people with stronger muscles live longer and have less difficulty standing, walking, and using the toilet when they get older (Rantanen et al. 1999; Ruiz et al. 2008). So, you join a fitness centre and hire a personal trainer. The trainer assesses your maximal strength, and then guides you through a 4-week program that involves lifting weights which are about 80% of your maximum.

Sure enough, after the program, you become stronger (probably around 20% stronger) (Carroll et al. 2011). You think this is great – and it is! You are so excited, you decide to stand in front of your mirror, flex your biceps, and take a selfie (your plan is to post the picture to Facebook to show your friends how much bigger your muscles got). However, after examining the picture, you realise your muscles did not get bigger. Or perhaps they did get a little bigger, but not enough to explain your substantial improvement in strength. You are somewhat disappointed in this, but then you remember your goal was to get stronger, not necessarily bigger, so you post the picture, anyway.

Magnetic stimulation of the brain can be used to test how well a person can voluntarily drive their muscles.

Interestingly, the observations you made are completely consistent with the scientific literature. Within the first weeks of strength training, muscle strength can improve without a change in the size or architecture of the muscle (e.g., Blazevich et al. 2007). Consequently, researchers have speculated that initial improvements in muscle strength from strength training are due primarily to changes in the central nervous system. One hypothesis has been that strength training helps the nervous system learn how to better “drive” or communicate with muscles. This ability is termed voluntary activation, and it can be tested by stimulating the motor area of an individual’s brain while they perform a maximal contraction (Todd et al. 2003). If the stimulation produces extra muscle force, it means that the individual’s nervous system was not maximally activating their muscles. Currently, there is no consensus as to whether voluntary activation can actually be improved by strength training.

Therefore, we conducted a randomised, controlled trial in which one group of participants completed four weeks of strength training, while a control group did not complete the training (Nuzzo et al. in press). For the group who performed the training, each exercise session consisted of four sets of strong contractions of the elbow flexor muscles (i.e., the muscles that bend the elbow, such as the biceps). Before and after the four week intervention, both groups were tested for muscle strength, voluntary activation, and several other measures. The participants were healthy, university-aged, and they had limited or no experience with strength training.

WHAT DID WE FIND?

Prior to the intervention, the strength training and control groups had similar levels of muscle strength and activation of the elbow flexor muscles. After the intervention, the group who performed the strength training improved their strength by 13%. They also improved their voluntary activation from 88.7% to 93.4%. The control group did not improve muscle strength or voluntary activation.

SIGNIFICANCE AND IMPLICATIONS

The results from our study show that four weeks of strength training improves the brain’s ability to “drive” the elbow flexor muscles to produce their maximal force. This helps to explain how muscles can become stronger, without a change in muscle size or architecture. Moreover, the results suggest that clinicians should consider strength training as a treatment for patients with motor impairments (e.g., stroke), as these individuals are likely to have poor voluntary activation (Bowden et al. 2014).

AUTHOR BIO

Jim Nuzzo is a Postdoctoral Fellow at Neuroscience Research Australia (NeuRA). His research investigates how strength training alters the neural connections between the brain and muscles. Click here to read Jim’s other blogs.

The Oxford dictionary defines the term priming as “a substance that prepares something for use or action.” In this special issue, we define motor priming as a technique, experience, or activity targeting the motor cortex resulting in subsequent changes in motor behavior. Inadequate functional recovery after neural damage is a persisting burden for many, and this insufficiency highlights the need for new neurorehabilitation paradigms that facilitate the capacity of the brain to learn and recover. The concept of motor priming has gained importance in the last decade. Numerous motor priming paradigms have emerged to demonstrate success to improve functional recovery after injury. Some of the successful priming paradigms that have shown to alter motor behavior and are easily implementable in clinical practice include non-invasive brain stimulation, movement priming, motor imagery, and sensory priming. The full clinical impact of these priming paradigms has not yet been realized due to limited evidence regarding neural mechanisms, safety and effectiveness, dosage, individualization of parameters, identification of the appropriate therapies that need to be provided in combination with the priming technique, and the vital time window to maximize the effectiveness of priming. In this special issue, four manuscripts address critical questions that will enhance our understanding of motor priming paradigms and attempt to bridge the gap between neurophysiology and clinical implementation.

In their study, “Non-Invasive Brain Stimulation to Enhance Upper Limb Motor Practice Poststroke: A Model for Selection of Cortical Site,” Harris-Love and Harrington elegantly address the extremely important issue of individualizing brain stimulation for upper limb stroke recovery. Many brain stimulation techniques show high interindividual variability and low reliability as the “one-size-for-all” does not fit the vast heterogeneity in recovery observed in stroke survivors. In this article, the authors propose a novel framework that personalizes the application of non-invasive brain stimulation based on understanding of the structural anatomy, neural connectivity, and task attributes. They further provide experimental support for this idea with data from severely impaired stroke survivors that validate the proposed framework.

The issue of heterogeneity poststroke is also addressed by Lefebvre and Liew in “Anatomical Parameters of tDCS to modulate the motor system after stroke: A review.” These authors discuss the variability in research using tDCS for the poststroke population. According to the authors, the most likely sources of variability include the heterogeneity of poststroke populations and the experimental paradigms. Individually based variability of results could be related to various factors including: (1) molecular factors such as baseline measures of GABA, levels of dopamine receptor activity, and propensity of brain-derived neurotropic factor expression; (2) time poststroke, (3) lesion location; (4) type of stroke; and (5) level of poststroke motor impairment. Variability related to experimental paradigms include the timing of the stimulation (pre- or post-training), the experimental task, and whether the protocol emphasizes motor performance (a temporary change in motor ability) or motor learning based (more permanent change in motor ability). Finally, the numerous possibilities of electrode placement, neural targets, and the different setups (monocephalic versus bi-hemispheric) add further complexity. For future work with the poststroke population, the authors suggest that tDCS experimental paradigms explore individualized neural targets determined by neuronavigation.

In another exciting study in this issue, Estes et al. tackle the timely topic of spinal reflex excitability modulated by motor priming in individuals with spinal cord injury. The authors choose to test four non-pharmacological interventions: stretching, continuous passive motion, transcranial direct current stimulation, and transcutaneous spinal cord stimulation to reduce spasticity. Three out of four techniques were associated with reduction in spasticity immediately after treatment, to an extent comparable to pharmacological approaches. These priming approaches provide a low-cost and low-risk alternative to anti-spasticity medications.

In another clinical study in individuals with spinal cord injury, Gomes-Osman et al. examined effects of two different approaches to priming. Participants were randomized to either peripheral nerve stimulation (PNS) plus functional task practice, PNS alone, or conventional exercise therapy. The findings were unexpected. There was no change in somatosensory function or power grip strength in any of the groups. Interestingly, all of the interventions produced changes in precision grip of the weaker hand following training. However, only PNS plus functional task practice improved precision grip in both hands. The authors found that baseline corticospinal excitability were significantly correlated to changes in precision grip strength of the weaker hand. The lack of change in grip strength in any of the groups was surprising. Previous evidence suggests, however, that the corticomotor system is more strongly activated during precision grip as compared to power grip, and the authors suggest that interventions targeting the corticomotor system (i.e., various priming methods) may more strongly effect precision grip.

Overall, this special issue brings together an array of original research articles and reviews that further enhance our understanding of motor priming for motor recovery with an emphasis on neural mechanisms and clinical implementation. We hope that the studies presented encourage future studies on motor priming paradigms to optimize the potential for functional recovery in the neurologically disadvantaged population, and further our understanding of neuroplasticity after injury.

Author Contributions

SM and MS have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Funding

SM is supported by funding from the National Institutes of Health (R01HD075777).

Having a Vagus Nerve Stimulator implanted can be a tough decision. Is it right for you? Will it work? What are the side effects and consequences?

I did some research and got the low-down on what it is, how it works and some interesting statistics. (If you are already acquainted with the VNS and are on the fence, you might want to just skip down to risks and benefits sections.)

How it works

Vagus Nerve Stimulation (VNS) has been used to treat more than 30,000 epilepsy patients worldwide. It’s designed to prevent or interrupt seizures or electrical disturbances in the brain for people with hard to control seizures. Used in conjunction with anti-seizure medications, the VNS uses electrical pulses that are delivered to the vagus nerve in the neck and travel up into the brain.

The good news is that the vagus nerve has very few pain fibers, so it’s…

New research from the University of Liverpool, published in the journal Brain, has highlighted the potential reasons why many patients with severe epilepsy still continue to experience seizures even after surgery.

Epilepsy continues to be a serious health problem and is the most common serious neurological disorder. Medically intractable temporal lobe epilepsy (TLE) remains the most frequent neurosurgically treated epilepsy disorder.

Many people with this condition will undergo a temporal lobe resection which is a surgery performed on the brain to control seizures. In this procedure, brain tissue in the temporal lobe is resected, or cut away, to remove the seizure focus.

Unfortunately, approximately one in every two patients with TLE will not be rendered completely seizure free after temporal lobe surgery, and the reasons underlying persistent postoperative seizures have not been resolved.

Reliable biomarkers

Understanding the reasons why so many patients continue to experience postoperative seizures, and identifying reliable biomarkers to predict who will continue to experience seizures, are crucial clinical and scientific research endeavours.

Researchers from the University’s Institute of Translational Medicine, led by Neuroimaging Lead Dr Simon Keller and collaborating with Medical University Bonn (Germany), Medical University of South Carolina (USA) and King’s College London, performed a comprehensive diffusion tensor imaging (DTI) study in patients with TLE who were scanned preoperatively, postoperatively and assessed for postoperative seizure outcome.

The results of these scans allowed the researchers to examine regional tissue characteristics along the length of temporal lobe white matter tract bundles. White matter is mainly composed of axons of nerve cells, which form connections between various grey matter areas of the brain, and carry nerve impulses between neurons allowing communication between different brain regions.

Through their analysis the researchers could determine how abnormal the white matter tracts were before surgery and how the extent of resection had affected each tract from the postoperative MRI scans.

The researchers identified preoperative abnormalities of two temporal lobe white matter tracts that are not included in standardised temporal lobe surgery in patients who had postoperative seizures but not in patients with no seizures after surgery.

The two tracts were in the ‘fornix’ area on the same side as surgery, and in the white matter of the ‘parahippocampal’ region on the opposite side of the brain.

The tissue characteristics of these white matter tracts enabled researchers to correctly identify those likely to have further seizures in 84% of cases (sensitivity) and those unlikely to have further seizures in 89% of cases (specificity). This is significantly greater than current estimates.

The researchers also found that a particular temporal lobe white matter tract called the ‘uncinate fasciculus’ was abnormal – and potentially involved in the generation of seizures – in patients with excellent and suboptimal postoperative outcomes.

However, it was found that significantly more of this tract was surgically resected/removed in the patients with an excellent outcome.

New insights

Dr Simon Keller, said: “There is scarce information on the prediction of postoperative seizure outcome using preoperative imaging technology, and this study is the first to rigorously investigate the tissue characteristics of temporal lobe white matter tracts with respect to future seizure classifications.

“Although there is some way to go before this kind of data can influence routine clinical practice, these results may have the potential to be developed into imaging prognostic markers of postoperative outcome and provide new insights for why some patients with temporal lobe epilepsy continue to experience postoperative seizures.”

By the time epilepsy patient Erika Fleck came to Loyola Medicine for a second opinion, she was having three or four seizures a week and hadn’t been able to drive her two young children for five years.

“It was no way to live,” she said.

Loyola epileptologist Jorge Asconapé, MD, recommended surgery to remove scar tissue in her brain that was triggering the seizures. Neurosurgeon Douglas Anderson, MD, performed the surgery, called an amygdalohippocampectomy. Ms. Fleck hasn’t had a single seizure in the more than three years since her surgery.

“I’ve got my life back,” she said. “I left my seizures at Loyola.”

Surgery can be an option for a minority of patients who do not respond to medications or other treatments and have epileptic scar tissue that can be removed safely. In 60 to 70 percent of surgery patients, seizures are completely eliminated, and the success rate likely will improve as imaging and surgical techniques improve, Dr. Anderson said.

Traditionally, patients would have to try several medications with poor results for years or decades before being considered for surgery, according to the Epilepsy Foundation. “More recently, surgery is being considered sooner,” the foundation said. “Studies have shown that the earlier surgery is performed, the better the outcome.” (Ms. Fleck is a service coordinator for the Epilepsy Foundation North/Central Illinois Iowa and Nebraska.)

Dr. Asconapé said Ms. Fleck was a perfect candidate for surgery because the scar tissue causing her seizures was located in an area of the brain that could be removed without damaging critical structures.

Ms. Fleck experienced complex partial seizures, characterized by a deep stare, unresponsiveness and loss of control for a minute or two. An MRI found the cause: A small area of scar tissue in a structure of the brain called the hippocampus. The subtle lesion had been overlooked at another center.

Epilepsy surgery takes about three hours, and patients typically are in the hospital for two or three days. Like all surgery, epilepsy surgery entails risks, including infection, hemorrhage, injury to other parts of the brain and slight personality changes. But such complications are rare, and they pose less risk to patients than the risk of being injured during seizures, Dr. Asconapé said.

Loyola has been designated a Level Four Epilepsy Center by the National Association of Epilepsy Centers. Level Four is the highest level of specialized epilepsy care available. Level Four centers have the professional expertise and facilities to provide the highest level of medical and surgical evaluation and treatment for patients with complex epilepsy.

Loyola’s comprehensive, multidisciplinary Epilepsy Center offers a comprehensive multidisciplinary approach to epilepsy and seizure disorders for adults and children as young as two years old. Pediatric and adult epileptologist consultation and state-of-the-art neuroimaging and electrodiagnostic technology are used to identify and assess complex seizure disorders by short- and long-term monitoring.

The research evoked 8,774 motor potentials (MEPs) that were elicited in six muscles of the upper and lower extremity by stimulating four gyri in patients with five possible tumor locations. Regarding the MEP frequency of each muscle-gyrus subdivision per patient, the expected frequency was 3.53 (8,774 divided by 100 patients, further divided by six muscles and four gyri). Accordingly, the patient ratio for each subdivision was calculated by defining the per-patient minimum data points as three.

The tumor-location specific patient ratios were higher for frontal tumors in both gyri than for other tumor locations. This suggests that the finger representation reorganization in these frontal gyri, which corresponds to location of dorsal premotor areas, might be due to within-premotor reorganization rather than relocation of motor function from PrG into premotor areas one might expect from the Rolandic tumors. The research indicates that reorganization of the finger motor representations might be limited along the middle-to-dorsal dimension of the dorsal premotor areas (posterior MFG and SFG) and might not cross rostrally from the primary motor cortex (PrG) to the dorsal premotor cortex.

Brain Derived Neurotrophic Factor (BDNF) has been referred to as a fertilizer for your brain. Find out how exercise can help you to get more of it.

Brain Derived Neurotrophic Factor (BDNF) has been referred to as a fertilizer for your brain. It is a substance that is found in your brain and helps to maintain the life of your brain cells, as well as grow new ones. You’ve probably heard all about ‘neuroplasticity’ and how we used to think our brains, once adult, were like a lump of concrete – unable to change and grow. Scientists now believe our brains are more like plastic – able to adapt, grow and change depending on what we do with them. BDNF is widely accepted as being a key player in this ‘plastic’ ability of the brain – its presence has been shown to make brain cells in petri dishes sprout new branches (necessary activity for a cell to make new connections!).

Low levels of BDNF have been associated with depression, anxiety, poor memory and brain degeneration as seen in conditions such as Alzheimer’s and dementia.

Why would you want more BDNF?

Improved learning and memory

May trigger the production of more serotonin (hello happy feelings!)

Helps with new skill acquisition

Improved mood (exercise increases BDNF as much or even more than taking antidepressants does)

Lower rates of Alzheimer’s disease and dementia in older age may be related to higher levels of BDNF.

Are you getting the picture? Better mood, better mental performance, healthier brain as you age…

How do you get more BDNF?

One word: STIMULATION. Stimulation of your brain and all its cells can come in many forms. Of course, traditional brain exercise has been thought of as activities such as cross words and Sudoku (which are definitely good!) but here’s another aspect you can add to the list: exercise. As little as 30 minutes of jogging on three days a week has been shown to improve brain functioning, but even better gains have been suggested with more complex activity, which requires you to build or acquire a skill. An example of this is exercise that challenges your balance or thinking, like rock climbing or dancing.

The ultimate brain booster? A bit of aerobic exercise (at least ten minutes) to increase levels of BDNF and other neurotransmitters, as well as all those other wonderful benefits of aerobic exercise, followed by a skill-based exercise to get the new brain cells creating new networks with each other.

TIP: Want to maximize the increased learning capacity of your brain? Don’t try to learn something while exercising (stop taking your study notes to the spin bike!) – blood flow increases to the brain post-exercise, while BDNF levels are still increased, meaning immediately after exercise is the perfect time to take in new information. Put on that French language podcast on the way home from the gym…

EXERCISE RIGHT’S FIVE FAVOURITE WAYS TO MOVE FOR MORE BDNF

1. Indoor rock-climbing – especially if you actively commute to the rock wall!

2. Trail running – something with twists, turns and great views is awesome

3. Dancing – where you’re learning new moves and also working your fitness

4. Functional movement – wait until the after school rush has finished then go check out (and play on) your nearest playground – think monkey bars, crawling through tunnels and balancing on beams

5. Team sports – they require you to be getting great aerobic gains by running around, whilst also working your brain in terms of strategy and quick thinking

There have been remarkable advances in understanding the brain, but how do you actually study the neurons inside it? Using gorgeous imagery, neuroscientist and TED Fellow Carl Schoonover shows the tools that let us see inside our brains.

The development of magnetic resonance imaging (MRI) is a success story for basic research. Today medical diagnostics would be inconceivable without it. But the research took time to reach fruition: it has been nearly half a century since physicists first began their investigations that ultimately led to what became known as nuclear magnetic resonance. In 2001, Nikos K. Logothetis and his colleagues at the Max Planck Institute for Biological Cybernetics in Tübingen devised a new methodological approach that greatly deepened our understanding of the principles of functional MRI.

The great advantage of functional magnetic resonance imaging (fMRI) is that it requires no major interventions in the body. In fMRI, the human body is exposed to the action of electromagnetic waves. As far as we know today, the process is completely harmless, despite the fact that fMRI equipment generates magnetic fields that are about a million times stronger than the natural magnetic field of the earth.

The physical phenomenon underlying fMRI is known as nuclear magnetic resonance, and the path to its discovery was paved with several Nobel prizes. The story begins in the first half of the 20th century with the description of the properties of atoms. The idea of using nuclear magnetic resonance as a diagnostic tool was mooted as early as the 1950s. But the method had to be refined before finally being realised in the form of magnetic resonance imaging.

Today, MRI not only produces images of the inside of our bodies; it also provides information on the functional state of certain tissues. The breakthrough for fMRI came in the 1980s when researchers discovered that MRI can also be used to detect changes in the oxygen saturation of blood, a principle known as BOLD (blood oxygen level dependent) imaging. There is a 20 percent difference between the magnetic sensitivity of oxygenated arterial blood and that of deoxygenated venous blood. Unlike oxygenated haemoglobin, deoxygenated haemoglobin amplifies the strength of a magnetic field in its vicinity. This difference can be seen on an MRI image.

Resuscitation of the brain after a 15-minute cardiac arrest in fMRI: The pictorial representation provides information about the degree of damage of the brain as well as a detailed analysis of the recovery curve. The top three rows are examples of successful and the bottom row for an unsuccessful resuscitation. The comparison with the concentration images of ATP, glucose and lactate shows that the MR images are in fact closely related to the biochemical changes. Based on such studies, the course of cerebral infarction and the success of various therapeutic measures can be documented. Credit Max Planck Institute.

fMRI has given us new insights into the brain, especially in neurobiology. However, the initial phase of euphoria was followed by a wave of scepticism among scientists, who questioned how informative the “coloured images” really are. Although fMRI can in fact generate huge volumes of data, there is often a lack of background information or basic understanding to permit a meaningful interpretation. As a result, there is a yawning gap between fMRI measurements of brain activity and findings in animals based on electrophysiological recordings.

This is due mainly to technical considerations: interactions between the strong MRI field and currents being measured at the electrodes made it impossible to apply the two methods simultaneously to bridge the gap between animal experiments and findings in humans.

fMRT shows input signals

In 2001, Nikos Logothetis and his colleagues at the Max Planck Institute for Biological Cybernetics in Tübingen were the first to overcome this barrier. With the help of special electrodes and sophisticated data processing, they showed unambiguously that BOLD fMRI actually does measure changes in the activity of nerve cells. They also discovered that BOLD signals correlate to the arrival and local processing of data in an area of the brain rather than to output signals that are transmitted to other areas of the brain. Their paper was a milestone in our understanding of MRI and has been cited over 2500 times worldwide.

Their novel experimental setup enabled the Tübingen scientists to study various aspects of nerve cell activity and to distinguish between action potentials and local field potentials. Action potentials are electrical signals that originate from single nerve cells or a relatively small group of nerve cells. They are all-or-nothing signals that occur only if the triggering stimulus exceeds a certain threshold. Action potentials therefore reflect output signals. These signals are detected by electrodes located in the immediate vicinity of the nerve cells. By contrast, local field potentials generate slowly varying electrical potentials that reflect signals entering and being processed in a larger group of nerve cells.

Applying these three methods simultaneously, the Max Planck researchers examined the responses to a visual stimulus in the visual cortex of anaesthetized monkeys. Comparison of the measurements showed that fMRI data relate more to local field potentials than to single-cell and multi-unit potentials. This means that changes in blood oxygen saturation are not necessarily associated with output signals from nerve cells; instead, they reflect the arrival and processing of signals received from other areas of the brain.

Another important discovery the Tübingen researchers made was that, because of the large variability of vascular reactions, BOLD fMRI data have a much lower signal-to-noise ratio than electrophysiological recordings. Because of this, conventional statistical analyses of human fMRI data underestimate the extent of activity in the brain. In other words, the absence of an fMRI signal in an area of the brain does not necessarily mean that no information is being processed there. Doctors need to take this into account when interpreting fMRI data.

Summary: Researchers report adult neurogenesis not only helps increase the number of cells in a neural network, it also promotes plasticity in the existing network. Additionally, they have identified the role the Bax gene plays in synaptic pruning.

Source: University of Alabama at Birmingham.

One goal in neurobiology is to understand how the flow of electrical signals through brain circuits gives rise to perception, action, thought, learning and memories.

Linda Overstreet-Wadiche, Ph.D., and Jacques Wadiche, Ph.D., both associate professors in the University of Alabama at Birmingham Department of Neurobiology, have published their latest contribution in this effort, focused on a part of the brain that helps form memories — the dentate gyrus of the hippocampus.

The dentate gyrus is one of just two areas in the brain where new neurons are continuously formed in adults. When a new granule cell neuron is made in the dentate gyrus, it needs to get ‘wired in,’ by forming synapses, or connections, in order to contribute to circuit function. Dentate granule cells are part of a circuit that receive electrical signals from the entorhinal cortex, a cortical brain region that processes sensory and spatial input from other areas of the brain. By combining this sensory and spatial information, the dentate gyrus can generate a unique memory of an experience.

Overstreet-Wadiche and UAB colleagues posed a basic question: Since the number of neurons in the dentate gyrus increases by neurogenesis while the number of neurons in the cortex remains the same, does the brain create additional synapses from the cortical neurons to the new granule cells, or do some cortical neurons transfer their connections from mature granule cells to the new granule cells?

Their answer, garnered through a series of electrophysiology, dendritic spine density and immunohistochemistry experiments with mice that were genetically altered to produce either more new neurons or kill off newborn neurons, supports the second model — some of the cortical neurons transfer their connections from mature granule cells to the new granule cells.

This opens the door to look at how this redistribution of synapses between the old and new neurons helps the dentate gyrus function. And it opens up tantalizing questions. Does this redistribution disrupt existing memories? How does this redistribution relate to the beneficial effects of exercise, which is a natural way to increase neurogenesis?

“Over the last 10 years there has been evidence supporting a redistribution of synapses between old and new neurons, possibly by a competitive process that the new cells tend to ‘win,’” Overstreet-Wadiche said. “Our findings are important because they directly demonstrate that, in order for new cells to win connections, the old cells lose connections. So, the process of adult neurogenesis not only adds new cells to the network, it promotes plasticity of the existing network.”

The study opens the door to look at how this redistribution of synapses between the old and new neurons helps the dentate gyrus function. NeuroscienceNews.com image is for illustrative purposes only.

“It will be interesting to explore how neurogenesis-induced plasticity contributes to the function of this brain region,” she continued. “Neurogenesis is typically associated with improved acquisition of new information, but some studies have also suggested that neurogenesis promotes ‘forgetting’ of existing memories.”

The researchers also unexpectedly found that the Bax gene, known for its role in apoptosis, appears to also play a role in synaptic pruning in the dentate gyrus.

“There is mounting evidence that the cellular machinery that controls cell death also controls the strength and number of synaptic connections,” Overstreet-Wadiche said. “The appropriate balance of synapses strengthening and weakening, collectively termed synaptic plasticity, is critical for appropriate brain function. Hence, understanding how synaptic pruning occurs may shed light on neurodevelopmental disorders and on neurodegenerative diseases in which a synaptic pruning gone awry may contribute to pathological synapse loss.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

All of the work was performed in the Department of Neurobiology at UAB. In addition to Overstreet-Wadiche and Wadiche, co-authors of the paper, “Adult born neurons modify excitatory synaptic transmission to existing neurons,” published in eLife, are Elena W. Adlaf, Ryan J. Vaden, Anastasia J. Niver, Allison F. Manuel, Vincent C. Onyilo, Matheus T. Araujo, Cristina V. Dieni, Hai T. Vo and Gwendalyn D. King.

Much of the data came from the doctoral thesis research of Adlaf, a former UAB Neuroscience graduate student who is now a postdoctoral fellow at Duke University.

Funding: Funding for this research came from Civitan International Emerging Scholars awards, and National Institutes of Health awards or grants NS098553, NS064025, NS065920 and NS047466.

Adult-born neurons are continually produced in the dentate gyrus but it is unclear whether synaptic integration of new neurons affects the pre-existing circuit. Here we investigated how manipulating neurogenesis in adult mice alters excitatory synaptic transmission to mature dentate neurons. Enhancing neurogenesis by conditional deletion of the pro-apoptotic gene Bax in stem cells reduced excitatory postsynaptic currents (EPSCs) and spine density in mature neurons, whereas genetic ablation of neurogenesis increased EPSCs in mature neurons. Unexpectedly, we found that Bax deletion in developing and mature dentate neurons increased EPSCs and prevented neurogenesis-induced synaptic suppression. Together these results show that neurogenesis modifies synaptic transmission to mature neurons in a manner consistent with a redistribution of pre-existing synapses to newly integrating neurons and that a non-apoptotic function of the Bax signaling pathway contributes to ongoing synaptic refinement within the dentate circuit.